Cannabis, cannabinoids and cancer – the evidence so far

We review and update this article as new research emerges. The last update was May 2018, where we made edits to the structure of the article to make the introduction and several sections clearer.

Few cancer topics spark as much online debate as cannabis.

The bottom line is that right now there isn’t enough reliable evidence to prove that any form of cannabis can effectively treat cancer in patients. This includes hemp oil, cannabis oil or the active chemicals found within the cannabis plant (cannabinoids) – whether natural or man-made.

Many researchers worldwide are actively investigating cannabinoids, and Cancer Research UK is supporting some of this work. These studies use highly purified chemicals found in the cannabis plant, or lab-made versions of them, and there is genuine interest in these as potential cancer treatments. But this is very different to street-bought cannabis and hemp oil available online or on the high street, for which there is no evidence of any impact on cancer.

Cannabis is still classified as a class B drug in the UK, meaning that it is illegal to possess or supply it. Cancer Research UK can’t comment on the legal status of cannabis, its use as a recreational drug, or its medical use in any other diseases. But we are supportive of properly conducted scientific research into cannabis and its derivatives that could benefit cancer patients.

Unfortunately, there are many unreliable sources of information about cannabis, particularly online. This post contains up-to-date, evidence-based information on cannabis and cancer, so with lots to cover, this is a long article. To help you find what you’re interested in, follow the links below to different sections. Or read on for everything you need to know about cannabis and cancer.

Cannabis and cannabinoids – what are they?

Cannabis has lots of names, including marijuana, pot, grass, weed, hemp, hashish or dope. Hemp oil is made from the seeds of a type of cannabis plant that doesn’t contain the main psychoactive ingredient, called delta-9 tetrahydrocannabinol (THC).

“Cannabinoids” is a blanket term covering a family of complex chemicals (both natural and man-made) that lock on to molecules on the surface of cells called cannabinoid receptors.

The human body also creates its own cannabinoid chemicals, known as endocannabinoids. Endocannabinoids, and the molecules they attach to (cannabinoid receptors), are involved in many systems and processes throughout the body, from appetite to the sensation of pain. Because of this molecular multitasking, they’re also linked to a huge range of illnesses, from cancer to neurodegenerative diseases.

Through many detailed experiments, summarised in this Nature Reviews Cancer article, scientists have discovered that both natural and synthetic cannabinoids have a wide range of effects on cells.

Can cannabinoids treat cancer?

Many hundreds of scientific papers looking at cannabinoids and cancer have been published, but these studies simply haven’t found enough robust scientific evidence to prove that these can safely and effectively treat cancer.

Research is still ongoing though, with hundreds of scientists investigating the potential of cannabinoids in cancer and other diseases as part of The International Cannabinoid Research Society. And in 2015 the scientific journal Nature published a supplement of review articles about various aspects of cannabis. It’s free to access.

Claims that there is solid “proof” that cannabis or cannabinoids can cure cancer is highly misleading to patients and their families, and builds a false picture of the state of progress in this area.

Virtually all the research into cannabinoids and cancer so far has been done in the lab.

This is because virtually all the scientific research investigating whether cannabinoids can treat cancer has been done using cancer cells grown in the lab or animals. Because humans are much more complex, these studies don’t necessarily hold true for people. That’s why so many promising results in the lab sadly don’t translate into safe or effective treatments when tested in humans.

So far, the best results from lab studies have come from using a combination of highly purified THC and cannabidiol (CBD), a cannabinoid found in cannabis plants that counteracts the psychoactive effects of THC. But researchers have also found positive results using man-made cannabinoids, such as a molecule called JWH-133.

There have been intriguing results from lab experiments looking at a number of different cancers, including glioblastoma brain tumours, prostate, breast, lung, and pancreatic cancers. But the take-home message is that different cannabinoids seem to have different effects on various cancer types, so they are far from being a ‘universal’ treatment.

Cannabis in clinical trials

To robustly test the potential benefits of cannabinoids in cancer, clinical trials in large numbers of people with control groups of patients – who aren’t given the treatment in question – would be needed.

Results have been published from only one small clinical trial testing whether cannabinoids can treat cancer in patients, led by Dr Manuel Guzman and his team in Spain. Nine people with advanced, incurable glioblastoma multiforme – the most aggressive brain tumour – were given highly purified THC through a tube directly into their brain.

This study showed that THC given in this way is safe and doesn’t seem to cause significant side effects, which suggests that cannabinoids could be worth pursuing in further clinical trials. But because this was an early stage trial without a control group, it couldn’t show whether THC helped to extend patients’ lives.

A handful of other clinical trials of cannabinoids for cancer are being set up. We’re helping to support the only two UK trials of cannabinoids for treating cancer, through our Experimental Cancer Medicine Centre (ECMC) Network. Both are at very early stages. One is testing a man-made cannabinoid called dexanabinol in patients with different types of advanced cancer. The second is testing whether Sativex (nabiximols), a highly purified pharmaceutical-grade extract of cannabis containing THC and CBD, can treat people with glioblastoma multiforme brain tumours that have come back after treatment.

Results from the second trial have now been released. These showed that combining Sativex with the chemotherapy temozolomide increased the number of patients who were alive one year after their brain tumour came back from 53% to 83%. This was a small trial with 21 patients taking part, so larger clinical trials are needed to confirm what the benefits of Sativex might be, and which patients are most likely to respond to this combination of treatments.

“But it worked for this patient…”

Doctors sometimes publish case reports about extraordinary or important observations they have seen in their clinic. For example, there is a published case report of a 14-year old girl from Canada who was treated with cannabis extracts (also referred to as “hemp oil”). But very little reliable information can be taken from a single patient treated with what’s an unknown mix of cannabinoids outside of a controlled clinical setting.

Dr Wai Liu at St George’s University is researching cannabis and cannabinoids for treating cancer (not funded by Cancer Research UK) to build up the evidence. He is happy to collect individual stories from UK patients and can be contacted by email. In the US, the Office of Cancer Complementary and Alternative Medicine gathers similar stories for their Best Case Series.

Unanswered questions

There are still many unanswered questions around the potential for using cannabinoids to treat cancer. It’s not clear:

which type of cannabinoid – either natural or synthetic – might be most effective

what kind of doses might be needed

which types of cancer might respond best to cannabinoids

how to avoid the psychoactive effects of THC

how best to get cannabinoids, which don’t dissolve easily in water, into cancer cells

whether cannabinoids will help to boost or counteract the effects of chemotherapy

These questions must be answered for cannabinoids to be used as safe and effective treatments for cancer patients. It’s the same situation for the many hundreds of other potential cancer drugs being developed and tested in university, charity and industry labs all over the world. Without doing rigorous scientific research, we will never sift the ‘hits’ from the ‘misses’. If cannabinoids are to get into the clinic, these hurdles first need to be overcome and their benefits proven over existing cancer treatments.

Can cannabis prevent or cause cancer?

There is no reliable evidence that cannabis can prevent cancer. There has been some research suggesting that endocannabinoids (mentioned earlier) can suppress tumour growth, and in experiments where mice were given very high doses of purified THC, they seemed to have a lower risk of developing cancer. But this is not enough solid scientific evidence to suggest that cannabinoids or cannabis can cut people’s cancer risk.

The evidence is a lot less clear when it comes to whether cannabis can cause cancer. This is because most people who use cannabis smoke it mixed with tobacco, a substance that we know causes cancer.

This complex issue hit the headlines in 2012 when the British Lung Foundation released a study suggesting that the cancer risks of cannabis had been underestimated, although this has been questioned by some experts, including Professor David Nutt.

What about controlling cancer symptoms such as pain or sickness?

There is good evidence that cannabinoids may be beneficial in managing cancer pain and side effects from treatment.

In some parts of the world, medical marijuana has been legalised for relieving pain and symptoms (palliative use), including cancer pain. But one of the problems with using herbal cannabis is managing the dose. Smoking cannabis or taking it in the form of tea often provides an inconsistent dose, which may make it difficult for patients to monitor their intake. So, researchers are turning to alternative dosing methods, such as mouth sprays, which deliver a reliable and regulated dose.

Large-scale clinical trials in the UK have been testing whether a mouth spray formulation of Sativex (nabiximols; mentioned earlier) can help to control severe cancer pain that doesn’t respond to other drugs. Results from these didn’t find any difference in self-reported pain scores between the treatment and the placebo.

Cannabinoids may also have potential in combating the loss of appetite and wasting (cachexia) experienced by some people with cancer, although so far clinical evidence is lacking. One clinical trial comparing appetite in groups of cancer patients given cannabis extract, THC and a placebo didn’t find a difference between the treatments, while another didn’t show any benefit and was closed early.

Is Cancer Research UK investigating cannabinoids?

Cancer Research UK has funded research into cannabinoids, notably the work of Professor Chris Paraskeva in Bristol investigating the properties of cannabinoids as part of his research into the prevention and treatment of bowel cancer. He has published a number of papers detailing lab experiments looking at endocannabinoids as well as THC, and written a review looking at the potential of cannabinoids for treating bowel cancer.

Our funding committees have previously received other applications from researchers who want to investigate cannabinoids but these failed to reach our high standards for funding. If we receive future proposals that meet these stringent requirements, then there is no reason that they wouldn’t be funded, assuming we have the money available.

Unfortunately, some scammers are using the email address ukcancerresearchcentre@gmail.com and claiming to be based at our head office, tricking cancer patients and their families into handing over money for “cannabis oil”, after which they receive nothing in return. This is a scam and has nothing to do with Cancer Research UK or our employees. If you believe you have been a victim of this fraud, please contact the police.

“It’s natural so it must be better, right?”

There’s no doubt that the natural world is a treasure trove of biologically useful compounds, and there are countless examples where these have been harnessed as effective treatments.

Numerous potent cancer drugs have also been developed in this way – purifying a natural compound, improving it and testing it to create a beneficial drug – including taxol, vincristine, vinblastine, camptothecin, colchicine, and etoposide. But although these purified drugs in controlled high doses can treat cancer, it doesn’t mean that the original plant (or a simple extract) will have the same effect. So, although cannabis contains certain cannabinoids, it doesn’t automatically follow that cannabis itself can treat cancer.

“Have you seen this video? This guy says cannabis cures cancer!”

There are many videos and anecdotes online claiming that people have been completely cured of cancer with cannabis, hemp/cannabis oil or other cannabis derivatives.

Despite what these sources may claim, it’s impossible to tell whether these patients have been ‘cured’ by cannabis or not. There is usually no information about their medical diagnosis, stage of disease, what other cancer treatments they had, or the chemical make-up of their treatment. These sources also only publish the “success stories”, and don’t share how many people who used cannabis or its derivatives had no benefit, or worse, were potentially harmed.

Robust scientific studies describe the detail of experiments and share the results – positive or negative. This is vital for working out whether a potential cancer treatment is truly safe and effective, or not. And publishing this data allows doctors around the world to judge the information for themselves and use it for the benefit and safety of their patients.

This is the standard to which all cancer treatments are held, and it’s one that cannabinoids should be held to, too.

“Are cancer charities hiding cannabis as a cure?”

Our aim is to beat cancer through research

We’ve blogged previously about how unjust this is to the thousands of scientists, doctors and nurses working as hard as they can to beat cancer, and to the many thousands of people in the UK and beyond who give up their time and money to fund our work.

History shows that the best way to beat cancer is through rigorous scientific research. This approach has helped to change the face of cancer prevention, diagnosis, treatment, leading to survival doubling over the past 40 years.

As a research-based organisation, we want to see reliable scientific evidence to support claims made about any cancer treatment, be it conventional or alternative. This is vital because lives are at stake. Some people may think that a cancer patient has nothing to lose by trying an alternative treatment, but there are big risks.

“What’s the harm? There’s nothing to lose.”

If someone chooses to reject conventional cancer treatment in favour of unproven alternatives, including cannabis, they may miss out on treatment that could save or significantly lengthen their life. They may also miss out on effective symptom relief to control pain or other problems.

Many of these unproven therapies are also expensive, and aren’t covered by the NHS or medical insurance. In the worst cases, an alternative therapy may even hasten death.

Although centuries of human experimentation tell us that naturally-occurring cannabinoids are broadly safe, they are not without risks. They can increase heart rate, which may cause problems for patients with pre-existing or undiagnosed heart conditions. They can also interact with other drugs in the body, including antidepressants and antihistamines. And they may also affect how the body processes certain chemotherapy drugs, which could cause serious side effects.

Cannabis is an illegal (class B) drug in the UK and there are further risks associated with using black market or home-made preparations, particularly cannabis oil, such as toxic chemicals left from the solvents used in the preparation process.

There are also many internet scams by people offering to sell cannabis preparations. As well as the risk of getting something with completely unknown chemical or medicinal properties and unknown effectiveness, scammers are tricking cancer patients and their families into handing over money for “cannabis oil” which they then never receive.

We understand the desire to try every possible avenue when conventional cancer treatment fails. But there is little chance that an unproven alternative treatment bought online will help, and it may well harm. We recommend that cancer patients talk to their doctor about clinical trials that they may be able to join, giving them access to new drugs in a safe and monitored environment.

“Big Pharma can’t patent it so they’re not interested.”

Some people argue that the potential of cannabinoids is being ignored by pharmaceutical companies, because they can’t patent the chemicals naturally occurring in cannabis plants. But there are many ways that these compounds can be patented – for example, by developing more effective lab-made versions or better ways to deliver them.

Other people argue that patients should be treated with ‘street’ or homegrown cannabis preparations, and that the research being done by companies is solely to make money and prevent patients accessing “the cure”.

But the best chance of ensuring that the potential benefits of cannabinoids – whether natural or man-made – can be brought to patients is through research using quality-controlled, safe, legal, pharmaceutical grade preparations containing known amounts of the drugs.

This requires time, effort and money, which may come from companies or independent organisations such as charities or governments. And, ultimately, this investment needs to be paid back by sales of a safe, effective new drug.

It’s true that there are issues around drug pricing and availability and we’re pushing for companies to make new treatments available at a fair price. We would hope that if cannabinoids were to be shown to be safe and effective enough to make it to the clinic, they would be made available at a fair price for all patients who might benefit from them.

“Why don’t you campaign for cannabis to be legalised?”

Cancer Research UK does not have an organisational policy on the legal status of cannabis, its use or abuse as a recreational drug, or its medical use in any other diseases. But we are supportive of properly conducted scientific research into cannabis and its derivatives that could benefit cancer patients and we will continue to monitor developments in the fields and evidence as it emerges.

In summary

Right now, there simply isn’t enough evidence to prove that cannabinoids – whether natural or synthetic – can effectively treat cancer in patients, although research is ongoing. And there’s certainly no evidence that ‘street’ cannabis can treat cancer.

We’re supportive of properly conducted scientific research into cannabis and its derivatives that could benefit cancer patients. Many researchers are actively exploring this approach, and Cancer Research UK is supporting, and will continue to support, scientifically robust research into cannabis and cannabinoids that reaches the high-quality standards set by our funding committees.

Kat

Public comments are closed on this post. If you have a considered comment you would like us to publish on this post you can contact the blog team at scienceblog@cancer.org.uk

We often see websites with long lists of scientific papers claiming that cannabis is a “cure” for various cancers. However, when we look at the detail of the data and the experimental detail of the research, it becomes clear that although they may be interesting and build evidence to show that cannabinoids may one day bring benefits for cancer patients, they are far from being a cure.

The main point to realise is that virtually all these studies have been done in cancer cells grown in the lab or in animals. These are quite artificial systems and are much less complex than a real cancer growing in a patient.

For example, most experiments with cells grown in the lab use cancer cells that were originally taken from a tumour many years ago, but have been grown for a long time in the lab – known as cell lines. One problem with such cells is that they are all very similar on a genetic and molecular level, but we know that in real cancers, the cells can be very different from each other and respond in different ways to treatments. Also the usual way of testing cannabinoids in animals has been done by transplanting cancer cells (either mouse or human) into mice. Usually only a small number (5-20) will be used for each experiment.

There’s growing evidence that these particular kinds of models (known as xenografts) aren’t as good at suggesting a treatment could work, compared to more sophisticated genetically engineered animals, as they don’t accurately represent the situation in real tumours. So although these kinds of experiments can point towards useful approaches, as well as revealing the underlying molecular ‘nuts and bolts’ of what’s going on, they can’t tell us if something will definitely treat cancer effectively and safely in human patients. They do not “prove that cannabis cures cancer”, as the headlines would have us believe.

Put simply, Petri dishes are not people. Most chemicals that show promise in lab or animal experiments turn out not to work as well as hoped when tested in patients. These kinds of human studies, known as clinical trials, are the only way we can really know if a cancer treatment is effective. There’s more about clinical trials on our website: http://www.cancerresearchuk.org/cancer-help/trials/types-of-trials/

It’s also important to think about what’s being claimed when people use the word “cure”. To most people, including us, this means that a cancer is completely treated and does not come back. When we look at the data in the papers listed below, none of them come close to showing these kinds of results. For the experiments involving cells grown in the lab, a proportion of the cells are killed or stop growing, but some of them carry on. Similarly in animal experiments, there is no data that shows a 100 per cent success rate for cannabinoids. For example, most mice treated with cannabinoids will still have tumours, although the cancers may be growing more slowly and spread less in some of them.

This isn’t just true for cannabinoids – it’s true for virtually all cancer drugs used today. Cancer is a very complex biological problem – there are hundreds of different types of cancer, each with important molecular and genetic differences. There’s good evidence to show that every individual’s cancer is as unique as they are, and that tumours can evolve and change within the body to become resistant to treatments.

We know that cancer drugs don’t work for everyone all the time – that’s why there’s so much effort going on to find more effective treatments – but it’s vital that doctors have a solid body of evidence showing how well the treatments they’re using are likely to work. If you or someone you loved were going to take any kind of drug, would you be happy if it had only been tested in very high doses on cancer cell lines grown in the lab, or in mice injected with cancer cells? Or would you want to know that it had been trialled in large numbers of people, and there was good data on how effective it is, whether it’s safe in the dose given, what the side effects are, and the proportion of people that can be expected to get better?

This kind of evidence can only come from a combination of lab studies leading to clinical trials. At the moment, while there are hundreds of interesting lab studies of cannabinoids (just some of which are included in the list below) there is only one clinical trial that has been published. So for now, cannabinoids, whether natural or synthetic, are a very long way from being what we would describe as a “cure” for any type of cancer.

We’ve looked at each of the papers in one of the commonly-seen lists (for example, here), and noted down the kinds of experiments they are. Many of them are available as open access papers, so it’s possible to look at the data for yourself. Hopefully this is a useful explanation of the kind of scientific research that is currently ongoing into cannabinoids and cancer, and the process of gathering evidence to show whether a potential cancer therapy works.

Brain Cancerhttp://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html These are the only published results of any clinical trial we are aware of testing cannabis for cancer, which we cover in the blog post. Nine people with advanced, terminal glioblastoma multiforme – an aggressive brain tumour – were given highly purified tetrahydrocannabinol (THC) through a tube directly into their brain. Eight people’s cancers showed some kind of response to the treatment, and one didn’t respond at all. All the patients died within a year, as might be expected for people with cancer this advanced.

http://mct.aacrjournals.org/content/10/1/90.abstract This is a study testing the combined effects of temozolomide, a drug used to treat brain tumours, with cannabinoids in brain tumour cells grown in the lab and also mice that have been transplanted with a human brain tumour cell line.

Breast Cancerhttp://www.ncbi.nlm.nih.gov/pubmed/20859676 This is a study with human breast cancer cell lines grown in the lab and mice that have been transplanted with mouse mammary (breast) cancer cells from a cell line.

http://www.ncbi.nlm.nih.gov/pubmed/21915267 This is a study looking at whether samples of human breast tumours carry the receptors for cannabinoids. The researchers also test the effects of a synthetic cannabinoid on human breast cancer cells lines grown in the lab, and in mice that have been transplanted with a breast cancer cell line.

http://cancerres.aacrjournals.org/content/66/13/6748.abstract This study looked at the effects of THC and a synthetic cannabinoid on two pancreatic cancer cells lines grown in the lab, and also in mice that had been transplanted with cells from a pancreatic cancer line. The researchers also show that human pancreatic cancer samples contain cannabinoid receptors.

http://www.ncbi.nlm.nih.gov/pubmed/22594963 This looks at the effects of non-THC cannabinoids (CBD and related compounds) on different human prostate cancer cell lines, and also on mice that have been transplanted with cells from two human prostate cancer lines.

Colorectal Cancerhttp://www.ncbi.nlm.nih.gov/pubmed/22231745 This looks at whether CBD can reduce the incidence of bowel cancer in mice that have been treated with a chemical that causes tumours. The researchers also looked at bowel cancer cell lines grown in the lab.

Ovarian Cancerhttp://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/1084 This is an abstract from research that was presented at a meeting, so it’s not possible to see the data or methods. From the abstract, it looks like the researchers have investigated the levels of cannabinoid receptors in human ovarian cancer cell lines grown in the lab, and also looked at the effects of a synthetic cannabinoid on these cell lines.

Blood Cancerhttp://www.ncbi.nlm.nih.gov/pubmed/12091357 This paper looks at a range of mouse and human leukaemia and lymphoma cell lines grown in the lab, looking for the presence of cannabinoid receptors and their response to THC or a synthetic cannabinoid. They also test the effects of THC on mice that have been transplanted with mouse lymphoma cells. Two out of eight mice were still alive at the end of the experiment.

http://molpharm.aspetjournals.org/content/70/5/1612.abstract This looks at the effects of an anandamide-like chemical and synthetic cannabinoids on lymphoma cell lines and samples of lymphoma from patients. It’s focusing on the molecular ‘nuts and bolts’ of what’s going on in the cells rather than testing how well they work.

Skin Cancerhttp://www.ncbi.nlm.nih.gov/pubmed/12511587 This paper looks at the effects of synthetic cannabinoids on mouse and human skin cancer cell lines grown in the lab, as well as mice that had been injected with mouse skin cancer cells – these were non-melanoma skin cancer cell lines, rather than melanoma. They also looked at the pattern of cannabinoid receptors in samples of human skin cancers.

Liver Cancerhttp://www.ncbi.nlm.nih.gov/pubmed/21475304 This paper looks at the effects of THC and a synthetic cannabinoid on human liver cancer cell lines grown in the lab. They also looked at the effects of these drugs on mice that had been transplanted with cells from a human liver cancer line.

Biliary Tract Cancerhttp://www.ncbi.nlm.nih.gov/pubmed/19916793 The link to this paper isn’t working so we’re unable to see the data or methods. From the abstract, it appears the researchers have tested THC on cholangiocarcinoma (bile duct cancer) cells grown in the lab, and also looked at patterns of cannabinoid receptors in samples of human bile duct tumours.

Bladder Cancerhttp://www.medscape.com/viewarticle/803983 This is a report from a scientific meeting looking at whether smoking cannabis affects bladder cancer risk. The data have not been published in a scientific journal so it isn’t possible to look at them in detail or draw any firm conclusions.

Cancer in Generalhttp://www.ncbi.nlm.nih.gov/pubmed/12514108 This paper looks at the effects of cannabinoids on blood vessel growth in tumours. The researchers test a synthetic cannabinoid on mice that have been transplanted with brain tumour cells, looking in particular at the tumour blood vessels, and also look at the effects of cannabinoids on human blood vessel cells growing in the lab.

http://www.ncbi.nlm.nih.gov/pubmed/15313899 This paper looks at how activity levels of certain genes in mouse brain tumours change when given a synthetic cannabinoid, focusing on genes involved in the growth of new blood vessels. The researchers also look at the effects of cannabinoids on human brain tumour cells and other cancer cells growing in the lab, and at certain molecular markers in tumour samples taken from patients involved in the clinical trial described in the first paper in this list (Guzman et al http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html )

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